Aptamers are nucleic acids that specifically associate with a ligand. Aptamers can be selected in vitro by a technique known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). SELEX is a method for optimizing nucleic acids for high-affinity to given ligands starting from random sequence libraries (Hermann T. and Patel D. J., February 2000, Science, Vol.287:820-825; Tuerk C. and Gold L., 1990, Science, Vol.249: 505).
Predominantly unstructured in solution, aptamers fold upon associating with their ligands into molecular architectures in which the ligand becomes specifically complexed with the nucleic acid. Because the evolutionary pressure on aptamer sequences during selection is directed primarily toward the binding of the ligands, the three-dimensional structures of aptamer complexes reflect highly optimized scaffolds for specific ligand recognition.
The architectures of aptamer complexes are valuable for the study of molecular recognition processes and yield a diversity of three-dimensional motifs, which recur in biologically relevant nucleic acid folds. It has been reported that small molecule RNA complexes are especially helpful for the rational exploration of RNA as a drug target. Drug design approaches for cellular RNA targets that combine structural data in RNA complexes with modelling techniques are especially promising, given the extraordinary success of molecular modelling of higher-order RNA architectures (Hermann and Patel, 2000). Nucleic acid aptamers provide unique tools in medicinal diagnosis and biotechnology and serve as therapeutics (Hermann and Patel, 2000). For example, aptamers that bind and inhibit human thrombin have been reported in Bock L. C. et al, 1992, Nature, Vol.355: 564-566.
However, there is a limitation in the use of aptamers because the structurally uniform four nucleotides are limited in possible alternative ways to pack around arbitrary ligands (Hermann and Patel, 2000).
There is therefore the need in this field of science of new solutions for the availability of aptamers which allow the selection of a highly diverse and differentiated kind of ligands.
The invention disclosed in the present application solves this problem in the art.